The goal of this project is to define the role of androgens and estrogens in the sexual differentiation process. Our working hypothesis is that defeminization (suppression of female-typical behaviors) and masculinization (enhancement of male-typical behaviors) are independent processes mediated by different hormonal regimes during development. To test this hypothesis, we will utilize androgen-insensitive testicular feminized (Tfm) mice and rats that differ in their responsiveness to androgens but not to estrogens. The Tfm mutants have a selected deficit in the androgen receptor-nuclear binding system but not in their estrogen receptor-nuclear binding system. We will compare differences and similarities in genotypes between species (rats vs mice) and within species (mutants vs littermates) to elucidate the relationship between specific hormone receptor-nuclear binding systems and the development of sexual behavior. Previous work has characterized the behavioral potential of the Tfm mice and rats. Now we will concentrate on the development of these behaviors. First, we will define the levels of circulating testosterone and aromatase activity during perinatal period of sexual differentiation. These assays can be routinely done in our laboratory. Our working hypothesis is that defeminization is mediated solely through the action of estrogen. Therefore, aromatase activity will be compared within genotypes that differ in behavioral defeminization. To identify which hormone(s) mediate the masculinization process, we will manipulate early hormonal stimulation. These studies will use aromatase inhibitors, androgen antagonists or hormone replacement in combination with neonatal castration. Parallel biochemical studies in perinatal rodents will determine whether our manipulations are having their putative effect. In addition, we will utilize females that carry the Tfm gene to dissect the relationship between hormone binding and responsiveness to androgens. Using the Tfm mutants together with endocrine manipulations and biochemical studies will provide unique information on the role of androgens and estrogens in differentiation of the neural systems underlying behavior.